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A Non-Comparative Study to Assess the Safety of MabThera (Rituximab) in Patients With Rheumatoid Arthritis.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00502996
First received: July 17, 2007
Last updated: August 22, 2016
Last verified: August 2016
  Purpose
This single arm study will assess the safety of MabThera plus methotrexate in patients with rheumatoid arthritis who have had a lack of response to 1-5 DMARDs or biological agents. Patients will receive MabThera (1g i.v.) on days 1 and 15, concomitantly with methotrexate >=15mg p.o./week. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: Methotrexate
Drug: rituximab [MabThera/Rituxan]
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Non-Comparative Expanded Access Program of to Assess Safety of Rituximab (Mab Anti Cd-20) in Patients With Rheumatoid Arthritis (Ser)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    An Adverse event (AE) was considered any unfavorable medical event in a participant of clinical research who received the study drug and that not necessarily had a causal relationship with this treatment. An AE could, therefore, being any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A serious adverse event (SAE) is any experience that suggested a significant risk, contraindication, caution, and at any dose fulfills at least one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment.

  • Number of Participants With AEs According to Degree of Intensity [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. The Intensity of AEs was classified as Grade 1, Grade 2, Grade 3 and Grade 4. Grade 1: Discomfort was noticed, but the normal daily activity was not interrupted. Grade 2: Discomfort was enough to reduce the normal daily activity. Grade 3: There was disability for work or develop normal daily activities. Grade 4: It represented an immediate threat to life (these events were reported as SAEs).

  • Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and SAEs [ Time Frame: Up to Week 48 ] [ Designated as safety issue: Yes ]
    An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A SAE is any experience that suggested a significant risk, contraindication, caution, and at any dose, fulfills, at least, one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment. Relationship between AEs and medication under investigation was evaluated through the classification "Yes" and "No". A relationship classified as "Yes" implied a significant causal relationship with the medication under investigation which was evaluated based on enough evidences, facts or arguments.

  • Number of Participants With AEs of Special Interest During the Study [ Time Frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) ] [ Designated as safety issue: Yes ]
    Adverse event of special interest during the study treatment and follow up period included infections. The participants with AEs of special interest were reported at Screening, End of treatment (EOT), and End of Follow-up (EOFU) visit.


Secondary Outcome Measures:
  • Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration) [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    The values of hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) for each participant were estimated at Screening and at EOT visit.

  • Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    The hematology parameters (hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, and basophils) for each participant were estimated at Screening and at EOT.

  • Mean Values of Hematology Parameter at Screening and EOT Visit (Mean Corpuscular Volume) [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    Mean corpuscular volume (MCV) is the average volume of red cells. The mean MCV concentration for each participant was estimated at Screening and EOT.

  • Mean Values of Hematology Parameter at Screening and EOT Visit (Erythrocytes) [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    The mean erythrocyte concentration for each participant was estimated at Screening and at EOT.

  • Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets) [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    The mean leucocytes and platelets concentration for each participant was estimated at Screening, at EOT visit.

  • Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose) [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    The mean albumin and glucose concentration for each participant was estimated at Screening and at EOT visit.

  • Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    The mean concentration of cholesterol, uric acid, urea, creatinine, calcium, total bilirubin and serum total proteins (STP) for each participant was estimated at Screening and at EOT visit.

  • Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    The mean concentration of potassium, chlorine, sodium and phosphorus for each participant was estimated at Screening and at EOT.

  • Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit [ Time Frame: Screening (Days -28 to 0) and EOT (Week 24) ] [ Designated as safety issue: No ]
    The mean aspartate transaminase (AST) and alanine transaminase (ALT), Alkaline phosphatase (AP), and Lactic dehydrogenase (LDH) concentration for each participant was estimated at Screening and at EOT visit.

  • Mean Duration of Morning Joint Stiffness [ Time Frame: Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48) ] [ Designated as safety issue: No ]
    The efficacy of rituximab was assessed by evaluating mean duration of morning joint stiffness.

  • Mean Value of Painful Joints [ Time Frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) ] [ Designated as safety issue: No ]
    The efficacy of rituximab was assessed by evaluating painful joints.

  • Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria [ Time Frame: Week 1, Week 12, and Week 24 ] [ Designated as safety issue: No ]
    American College of Rheumatology (ACR) criteria improvement consisting of 20%, 50%, and 70% (ACR20, ACR50, and ACR70, respectively) reduction in tender joints and swollen joints, as well as for three of the additional five ACR core set variables: patient's assessment of pain using a Visual Analog Scale (VAS) with left end of the line 0=no pain to right end of the line 100=unbearable pain); patient's global assessment of disease activity and physician's global assessment of disease activity using a VAS (0=no disease activity to 100=maximum disease activity); health assessment questionnaire (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant; C-reactive protein and globular sedimentation velocity.

  • Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index) [ Time Frame: Screening (Days -28 to 0), Week 1, Week 12, and Week 24 ] [ Designated as safety issue: No ]
    Health Assessment Questionnaire - Disease Index (HAQ-DI) indicates how the disease affected participant's activities of daily life. It consisted of 20 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale, 0=without any difficulty to 3=unable to do. Sum of scores was divided by number of domains with a score for a total possible score of 0 (best/no difficulties to perform activities) to 3 (worst/ unable to perform activities at all).

  • Mean Values of C Reactive Protein [ Time Frame: Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48) ] [ Designated as safety issue: No ]
    C Reactive Protein (CRP) is a component of ACR. CRP is a marker of inflammation.

  • Mean Values of Globular Sedimentation Velocity [ Time Frame: Screening ((Days -28 to 0), Week 1, Week 12, and Week 24 ] [ Designated as safety issue: No ]
    Globular sedimentation velocity is a component of ACR.

  • Mean Values of Pain and Activity Based on Visual Analogue Scale [ Time Frame: Screening ((Days -28 to 0), Week 1, Week 12, and Week 24 ] [ Designated as safety issue: No ]
    Pain assessment was assessed by using a VAS (0=no pain to 100=unbearable pain). Disease activity was also evaluated by participants and investigators by using a VAS (0=no disease activity to 100=maximum disease activity).

  • Mean Value of Inflamed Joints [ Time Frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) ] [ Designated as safety issue: No ]
    The efficacy of rituximab was assessed by evaluating inflamed joints.


Enrollment: 246
Study Start Date: February 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
Eligible participants receiving Rituximab (MabThera/Rituxan) 1 gram/dose (g/dose) intravenously (IV) on Day 1 and Day 15 followed by previous pre-medication (methylprednisolone 100 mg IV, antihistamine and antipyretic) and concomitant treatment of Methotrexate at least 15 mg per oris (PO) weekly were observed during the study period of 24 weeks. After treatment completion, participants were followed-up for safety up to 24 weeks.
Drug: Methotrexate
>=15 mg po/week
Drug: rituximab [MabThera/Rituxan]
1g iv on days 1 and 15

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • rheumatoid arthritis >=6 months;
  • lack of response to 1-5 DMARDs or biological agents;
  • rheumatoid factor positive.

Exclusion Criteria:

  • other chronic inflammatory articular disease or systemic rheumatic disease;
  • joint or bone surgery during 8 weeks prior to randomization;
  • previous treatment with any cell-depleting therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00502996

  Hide Study Locations
Locations
Argentina
Buenos Aires, Argentina, 1425
Buenos Aires, Argentina, C1280AEB
Buenos Aires, Argentina, C1426AAL
Córdoba, Argentina, 5000
San Miguel de Tucuman, Argentina, 4000
Tucuman, Argentina, 4000
Brazil
Belem, Brazil, 66063-240
Brasilia, Brazil, 70322000
Brasilia, Brazil, 70390-904
Campinas, Brazil, 13015-001
Campinas, Brazil, 13025-141
Curitiba, Brazil, 80730-000
Florianopolis, Brazil, 88040-970
Fortaleza, Brazil, 60155-290
Fortaleza, Brazil, 60430-370
Goiania, Brazil, 74110010
Nova Lima, Brazil, 34000-000
Porto Alegre, Brazil, 90610-000
Recife, Brazil, 50000-000
Ribeirão Preto, Brazil, 14048-900
Rio de Janeiro, Brazil, 20551-030
Rio de Janeiro, Brazil, 21941-590
Rio de Janeiro, Brazil, 22050-000
Rio de Janeiro, Brazil, 22640102
Salvador, Brazil, 40050-410
Sao Paulo, Brazil, 03128-050
Sao Paulo, Brazil, 04026-000
Sao Paulo, Brazil, 04038-002
Sao Paulo, Brazil, 04038-040
Sao Paulo, Brazil, 04039-004
Sao Paulo, Brazil, 05403-000
Vitoria, Brazil, 29043-910
Chile
Santiago, Chile
Colombia
Barranquilla, Colombia
Bogota, Colombia
Ecuador
Cuenca, Ecuador, 1394
Guayaquil, Ecuador
Quito, Ecuador, 1394
El Salvador
San Salvador, El Salvador
Mexico
Mexico City, Mexico, 02990
Mexico City, Mexico, 06920
Mexico City, Mexico, 14080
San Luis Potosi, Mexico, 78240
Peru
Jesus Maria, Peru
Lima, Peru, 13
San Isidro, Peru, LIMA 27
Uruguay
Montevideo, Uruguay, 11600
Venezuela
Barquisimeto, Venezuela, 3005
Caracas, Venezuela, 1010
Caracas, Venezuela, 1040
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00502996     History of Changes
Other Study ID Numbers: ML19385 
Study First Received: July 17, 2007
Results First Received: June 29, 2016
Last Updated: August 22, 2016
Health Authority: Mexico: Ministry of Health

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Methotrexate
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on December 08, 2016